Quantification of pain in sickle mice using facial expressions and body measurements

Abstract

Pain is a hallmark feature of sickle cell disease (SCD). Subjects typically quantify pain by themselves, which can be biased by other factors leading to overtreatment or under-treatment. Reliable and accurate quantification of pain, in real time, might enable to provide appropriate levels of analgesic treatment. The mouse grimace scale (MGS), a standardized behavioral coding system with high accuracy and reliability has been used to quantify varied types of pain. We hypothesized that addition of the objective parameters of body length and back curvature will strengthen the reproducibility of MGS. We examined MGS scores and body length and back curvature of transgenic BERK sickle and control mice following cold treatment or following treatment with analgesic cannabinoid CP55,940. We observed that sickle mice demonstrated decreased length and increased back curvature in response to cold. These observations correlate with changes in facial expression for the MGS score. CP55,940 treatment of sickle mice showed an increase in body length and a decrease in back curvature concordant with MGS scores indicative of an analgesic effect. Thus, body parameters combined with facial expressions may provide a quantifiable unbiased method for objective measure of pain in SCD.

CaMKIIα underlies spontaneous and evoked pain behaviors in Berkeley sickle cell transgenic mice

“…2B). Consistent with the findings from other cold pain measurements from other investigators, 24,34 these observations demonstrated the existence of cold-induced hypersensitivity in BERK mice.…”

“…49 Another group observed changes in mouse facial expression, body length and back curvature in response to noxious cold (4 °C). 34 Together with the findings of the current study, it is clear that BERK mice exhibited hypersensitivity to both mild and extremely cold stimuli, which was also reported by patients with SCD. 2,12,35 …”

Sensitization of C-fiber nociceptors in mice with sickle cell disease is decreased by local inhibition of anandamide hydrolysis

“…Patients with SCD had decreased pain thresholds for heat and cold stimuli [10]. Consistent with patient reports, hyperalgesia to cold and heat occurs in HbSS-BERK sickle mice [12,38,27,48,65]. In our study, C-fiber nociceptors sensitive to heat stimuli did not show lower thresholds but cumulative responses were higher than those in HbAA mice.…”

Sickle cell disease: a natural model of acute and chronic pain

“…SCD mice also express deep tissue, non-stimulus evoked pain, and musculoskeletal pain measured by decreased grip force strength, decreased voluntary wheel running[22; 29], altered grimace, body length and stature scores associated with chronic pain[41], and anxiety and depression-like behaviors[29; 31] which correlate the comorbidities of depression and anxiety in SCD patients. [57; 60] Female and male mice exhibit similar magnitudes of hypersensitivity[23], consistent with both female and male patients enduring the severe pain.…”